Cerebrospinal fluid (CSF) concentrations of homovanillic acid, 5- hydroxy indoleacetic acid, norepinephrine and 3-methoxy 4- hydroxphenyl ethylene glycol did not differ significantly between patients with Alzheimer's disease and age matched controls, and were not correlated with age in healthy men. CSF concentrations of choline increased with age in healthy men, and were higher in young adults with Down syndrome than in age matched controls. CSF biopterin, a coenzyme for tyrosine and tryptophan hydroxylase, was lower in patients with Alzheimer's disease that in controls, and was correlated with concentrations of 5-hydroxy- indoleacetic acid and homovanillic acid. Subtypes of Alzheimer's disease were identified: dementia of the Alzheimer type with extrapyramidal signs (EDAT), and with myoclonus (MDAT). The reductions in CSF acetylcholinesterase and somatostatin found in Alzheimer's disease were also found in EDAT and MDAT. However, these latter groups have additional deficits in monoamine markers; EDAT and MDAT have reduced CSF levels of homovanillic acid and biopterin, and additionally, MDAT is characterized by reductions in 5-hydroxy-indoleacetic acid. Corticotropin releasing hormone, a neuropeptide, was significantly reduced in the cerebrospinal fluid of patients with Alzheimer's disease as compared to controls, as was peptidyl alpha-amidation activity, suggesting a loss of neurons which produce amidated neuropeptides. CSF concentrations of other brain substances, including acetylcholinesterase, somatostatin, neuropeptide Y, alpha-melanocyte stimulating hormone, and polyols have also been measured. Ratios of albumin and immunoglobulin between cerebrospinal fluid and plasma were normal in Alzheimer's patients, suggesting that there is not a gross breakdown of the blood-brain barrier.